Granulomatous Iritis (Anterior Uveitis) 

Updated: Sep 19, 2018
Author: Andrew A Dahl, MD, FACS; Chief Editor: Hampton Roy, Sr, MD 

Overview

Background

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.

Pathophysiology

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.

Epidemiology

Frequency

United States

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.[1] However, these cases were predominantly nongranulomatous anterior uveitis.

International

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).

Mortality/Morbidity

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 due to chronic angle closure.

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, optic neuropathy) may result in severe vision loss.

Race

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 (VKH disease), although a rare cause of uveitis in the United States, is much more prevalent in persons of Mestizo, Asian, or American Indian ancestry.

Sex

No significant sex differences are reported.

Age

Granulomatous iritis may develop in individuals of any age.

Prognosis

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.

Patient Education

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

 

Presentation

History

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:

  • Pain: Some patients have no ocular pain, or they may describe a foreign body sensation. Other patients describe an abrupt onset of dull, aching eye pain. This pain may be ocular, or it may be referred to the periorbital region or temple.

  • Photosensitivity: Light, especially sunlight, worsens the discomfort, particularly with exacerbations.

  • Redness: Patients may describe having an injected eye. A discharge is usually not present.

  • Vision: The patient may have reduced visual acuity and may complain of floaters.

  • Granulomatous iritis is more likely to be a bilateral process (except in herpetic iridocyclitis), whereas nongranulomatous iritis is typically unilateral.

Physical

A complete ocular examination is indicated, including dilation of the pupil and careful examination of the retinal periphery.

Vision

Visual acuity may range from normal to significantly reduced, depending on the extent of the ocular inflammation and complications such as cataract, glaucoma, and cystoid macular edema.

Intraocular pressure (IOP)

IOP is usually reduced in the eye with iritis due to decreased aqueous production by the inflamed ciliary body. Occasionally, IOP is elevated as a result of altered or obstructed aqueous outflow. Increased intraocular pressure at the onset may suggest a viral etiology, particularly in unilateral disease.

External findings

Examine the patient for enlarged lacrimal glands and parotid glands and seventh cranial nerve palsy, as this may suggest sarcoidosis.

Conjunctiva

Generalized redness of the bulbar conjunctiva may be present. The eye may have perilimbal injection, termed ciliary flush. Carefully examine the patient for small conjunctival nodules that, if sampled during biopsy, may help in determining the underlying cause of the iritis. Perilimbal vitiligo (Sugiura's sign) is a sign of chronic Vogt-Koyanagi-Harada disease, occurring within a month of disease onset. It can be found in up to 85% of Japanese patients with Vogt-Koyanagi-Harada disease but is rarely seen in whites.

Cornea

Keratic precipitates (KPs) are found on the endothelium. KPs are clusters of white blood cells. The KPs seen in granulomatous iritis are significantly larger than those observed in nongranulomatous iritis, where cells tend not to clump together on the corneal endothelium. Mutton-fat KPs are large and have a greasy appearance. They are usually located over the lower half of the cornea. Corneal edema may be present. Corneal endotheliitis is a clinical entity manifested by corneal edema, keratic precipitates, and mild anterior chamber reaction, and can be defined as a spectrum of the disorder in which the corneal endothelium is the primary site of the inflammation. Viral infections including herpes simplex virus (HSV), varicella zoster virus, and cytomegalovirus can lead to corneal decompensation.[5]

Mutton-fat keratic precipitates in sarcoidosis. Mutton-fat keratic precipitates in sarcoidosis.

Anterior chamber

Flare and cells are usually present.

A 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:[2]

  • 0 = None

  • 1+ = Faint

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

  • 3+ = Marked (iris and lens details 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 1-mm field of light, as described by The SUN Working Group Grading Scheme for Anterior Chamber Cells, as follows:.

  • 0 < 1 cell

  • 0.5 = 1-5 cells

  • 1+ = 6-15 cells

  • 2+ = 16-25 cells

  • 3+ = 26-50 cells

  • 4+ = More than 50 cells

Iris

Peripheral anterior synechiae and posterior synechiae may be present. Inflammatory nodules on the iris (Koeppe and Busacca) are usually tan in color and represent accumulations of inflammatory cells. Koeppe nodules are found at the pupillary border. Busacca nodules are located on the surface of the iris. If Busacca nodules are present, then the underlying etiology is almost always a granulomatous process. These nodules are shown in the images below.

Granulomatous anterior uveitis with mutton-fat ker 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 Busac Granulomatous anterior uveitis with numerous Busacca nodules on the iris surface and a few mutton-fat keratic precipitates on the inferior aspect of the cornea.

Lens and 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 or ongoing chronic inflammation. Carefully examine the vitreous for inflammatory cells; if present, they imply a more extensive uveitic syndrome.

Posterior segment

Carefully examine the posterior segment through the dilated pupil for evidence of optic nerve edema, for vasculitis, and for focal retinal and/or choroidal lesions. A patient with a granulomatous-appearing iritis is likely to have a more extensive uveitis.

Causes

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.

  • Sarcoidosis

  • Syphilis

  • Vogt-Koyanagi-Harada disease

  • Sympathetic ophthalmia

  • Multiple sclerosis

  • Lyme disease

  • Tuberculosis

  • Herpes zoster

  • HSV

  • Acute retinal necrosis (ARN)

  • Cytomegalovirus (CMV)

  • Coccidioidomycosis

  • Leprosy

  • Toxoplasmosis

  • Brucellosis

  • Idiopathic

 

DDx

Differential Diagnoses

 

Workup

Laboratory Studies

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.

Laboratory tests are as follows:

  • Purified protein derivative (PPD) test or Quantiferon testing for TB

  • Chest radiograph for sarcoidosis and TB should be obtained. However, the chest radiograph is not very sensitive or specific for sarcoidosis and a high-resolution chest CT should be considered if sarcoidosis is strongly suspected. Gallium scan can also be considered for sarcoidosis.

  • Venereal Disease Research Laboratory (VDRL) test, FTA-ABS (or similar treponemal specific serology) test for syphilis A specific antitreponemal test must be obtained, as RPR or VDRL can provide false-negative results on RPR or VDRL.

  • CBC with differential

  • Angiotensin-converting enzyme (ACE) test for sarcoidosis may be obtained but is not very sensitive or specific, especially in children.

  • Anergy evaluation for sarcoidosis (rarely done)

  • Lyme serology if Lyme disease is suspected (eg, endemic area, tick bite, systemic manifestations)

  • Toxoplasmosis enzyme-linked immunosorbent assay (ELISA) if posterior uveitis associated

  • Antineutrophil cytoplasmic autoantibodies: c-ANCA with PR3 specificity is most specific for Wegener granulomatosis. c-ANCA is found in 80-95% of active cases. An isolated anterior uveitis (without orbital, scleral, or corneal involvement) is a very rare presentation of Wegener granulomatosis.

  • Cytology, polymerase chain reaction, and cultures of intra-ocular fluid when infection or masquerade suspected

  • In cases of suspected ARN, anterior chamber fluid and/or vitreous should be examined via polymerase chain reaction (PCR) for HSV and herpes zoster virus nucleic acid.

Imaging Studies

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.[6]

Ultrasonography (B scan) of the eye is performed if the posterior segment cannot be seen.

Procedures

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).

Histologic Findings

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

Medical Care

Treatment of inflammation of the anterior segment is discussed below.

Cycloplegia

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.

Corticosteroids

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

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.

Surgical Care

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 should 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.

Consultations

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.

Complications

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.

Further Outpatient Care

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.

 

Medication

Medication Summary

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.[7]

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

Corticosteroids

Class Summary

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

Prednisolone acetate 1% (Pred Forte, Econopred)

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

Prednisone (Meticorten, Deltasone, Orasone)

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.

Cycloplegia

Class Summary

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

Cyclopentolate hydrochloride 1% (AK-Pentolate, Cyclogyl)

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.