Signs and Symptoms

Uveitis may be noted in individuals of any age, but is most commonly encountered in those between 20 and 60 years of age.1,2 Anterior uveitis does not tend to favor either gender, nor is there any particular racial predilection.2,3 Patients with anterior uveitis typically present with complaints of pain, photophobia and hyperlacrimation. The pain is characteristically described as a deep, dull ache, which may extend to the surrounding orbit. Associated sensitivity to lights may be severe, and, often, these patients will present wearing dark sunglasses. Excessive tearing results secondary to increased neural stimulation of the lacrimal gland.

Visual acuity is variably affected. In the earliest stages of anterior uveitis, visual acuity is minimally compromised; however, as the condition persists over days to weeks, accumulation of cellular debris in the anterior chamber and along the corneal and lenticular surfaces may result in subjectively blurred vision.4,5 Accommodative tasks may be difficult or painful due to ciliary spasm. The patient with anterior uveitis may display a sluggish, fixed and/or irregular pupil on the involved side. Ocular motility is generally intact. Gross observation may reveal a pseudoptosis secondary to photophobia. There typically no notable lid edema.5

Clinical inspection of patients with uveitis typically reveals a deep perilimbal injection of the conjunctiva and episclera, although the palpebral conjunctiva remains unaffected. The cornea displays mild stromal edema upon biomicroscopy, and in more severe or protracted reactions, keratic precipitates may be noted on the endothelium. In nongranulomatous cases, these small, irregular gray to brown deposits with a predilection for the central or inferior cornea can be observed without large depositions (“mutton fat” keratic precipitate).5

The hallmark signs of nongranulomatous anterior uveitis are “cells and flare.” Cells represent leukocytes liberated from the iris vasculature in response to inflammation and are observable and freely floating in the convection currents of the aqueous. Flare is the term used to describe proteins liberated from the inflamed iris or ciliary body. When present, flare gives the aqueous a particulate, or smoky, appearance. When the inflammation is profound and the anterior chamber seems to be smothered in a cellular slurry, the condition is referred to as plasmoid aqueous. In the worst cases, such as those seen in endophthalmitis, the white blood cells will settle, creating what is known as hypopyon uveitis. Whenever there are sufficient cells in the anterior chamber, convection currents have the ability to carry some cells behind the iris into the anterior vitreous. This is termed spillover and must be differentiated from an intermediate or posterior uveitis.

Iris findings may include adhesions to the lens capsule (posterior synechia) or, less commonly, to the peripheral cornea (peripheral anterior synechia, PAS). Synechiae are the cause of irregular or fixed pupils in cases of uveitis. Additionally, granulomatous nodules are sometimes seen at the pupillary border (Koeppe nodules) and within the iris stroma (Bussaca nodules) in cases of uveitis associated with systemic disease.5,6

IOP is often impacted; it may be depressed, normal or elevated depending on the stage of presentation and the duration of the disease process. In early stages, IOP is characteristically reduced due to secretory hypotony of the inflamed ciliary body.5 However, as the reaction persists, inflammatory by-products may accumulate in the trabeculum, which can cause normalization at first, and elevation of IOP later. In severe cases, sustained IOP elevation signals the presence of uveitic glaucoma with increased potential for PAS and secondary angle closure.5,7 Elevated IOP may also occur as a consequence of prolonged topical corticosteroid therapy for anterior uveitis, but this is encountered only in a small percentage of patients.8-10


Uveitis should be thought of not as a singular ocular disorder, but rather as a diverse collection of pathological conditions with similar, clinically observable signs. A vast multitude of etiologies may induce uveitis, ranging from blunt trauma to widespread systemic infection (e.g., tuberculosis) to generalized ischemic disorders (e.g., giant cell arteritis).11-16 Some other well-known systemic etiologies include ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis, sarcoidosis, systemic lupus, Behçet’s disease, inflammatory bowel disease, multiple sclerosis, syphilis, Lyme disease, histoplasmosis and herpetic diseases.15,16 Of course, not all forms of uveitis are associated with identified systemic illness. Localized inflammations may occur as well, either by iatrogenic or idiopathic means. Some primary uveitic syndromes include Fuch’s heterochromic iridocyclitis and Posner-Schlossman syndrome (technically a trabeculitis).5,16

While the precise pathophysiology of anterior uveitis is not entirely clear, the cascade of events during this inflammatory state can be reasonably explained. In the normal human eye, the anterior chamber remains free of cells and plasma proteins by virtue of the blood/aqueous barrier. The blood/aqueous barrier is comprised of tight junctions between the endothelial cells of the iris vasculature and between the apico-lateral surfaces of the nonpigmented epithelium of the ciliary body.17 In an inflamed ocular state, cytokines mediate numerous tissue changes, among them vasodilation and increased vascular permeability.18,19 When the uveal vessels dilate, plasma, white blood cells and proteins exude into the extravascular spaces (e.g., the anterior chamber). Small molecular weight proteins may cloud the ocular media, but have little impact otherwise; however, as larger molecular weight proteins, such as fibrinogen, accumulate in the aqueous or vitreous, pathological sequelae follow. Fibrinogen is ultimately converted into fibrin, an insoluble protein involved in the blood-clotting process. In the anterior chamber, fibrin acts like glue, binding with cellular debris to form keratic precipitates. More importantly, fibrin facilitates the adhesion of adjacent ocular structures, forming synechiae.7 With synechiae comes the risk of secondary glaucomas, particularly angle closure with or without pupillary block.7 Additionally, chronic uveal inflammation results in an increased concentration of vasoproliferative mediators, promoting angiogenesis or neovascularization.18-20 Neovascular changes in the iris and angle can further predispose the uveitic eye to secondary glaucoma.


The primary goals in managing anterior uveitis are threefold: (1) immobilize the iris and ciliary body to decrease pain and prevent exacerbation of the condition; (2) quell the inflammatory response to avert detrimental sequelae; and (3) identify the underlying cause. Cycloplegia is a crucial step in achieving the first goal. This may be accomplished using a variety of topical medications. Depending on the severity of the reaction, practitioners may employ 5% homatropine BID-QID or 1% atropine QD-TID. Cyclopentolate is typically not potent enough to achieve adequate cycloplegia in the inflamed eye, and hence should be avoided.

Topical corticosteroids are used to address the ocular inflammatory response. For many years, the “gold standard” for uveitis management was 1% prednisolone acetate, ideally obtained in its branded form, PredForte (Allergan). In recent years however, many clinicians have recognized the utility of Durezol (0.05% difluprednate, Alcon) in controlling anterior uveitis.21-23 Clinical trials have demonstrated that Durezol can be dosed at roughly half the frequency as 1% prednisolone acetate while achieving the same clinical efficacy.22,23 Topical corticosteroids should be administered in a commensurate fashion with the severity of the inflammatory response. In pronounced cases, dosing every 15 to 30 minutes may be appropriate; however, at minimum, steroids should be instilled every three to four hours initially.

In cases where there are associated posterior synechiae, attempts can be made to break the adhesions in-office using 1% atropine in conjunction with 10% phenylephrine.24 Secondary elevations in IOP may be addressed by using aqueous suppressant anti-glaucoma agents such as beta blockers, carbonic anhydrase inhibitors and alpha adrenergic agonists. Miotics are contraindicated in the treatment of uveitic glaucoma, as they can worsen the inflammatory response by mobilizing the uveal tissues and disrupting the blood-aqueous barrier.7 Likewise, many physicians tend to avoid topical prostaglandin analogs after early reports that these IOP-lowering agents showed limited efficacy in the face of inflammation, and perhaps even exacerbated the uveitic response.25 However, other studies suggest that prostaglandin analogs are indeed both safe and effective in cases of uveitic glaucoma, with their principle disadvantage being length of time to adequate pharmacologic effect.26-28

After treatment is initiated, patients should be re-evaluated every one to seven days, depending on the severity of the reaction. As resolution becomes evident, cycloplegics may be discontinued and topical steroids may be tapered to QID or TID. It is generally advisable to taper slowly rather than abruptly, and patients may need to remain on steroid drops daily or every other day for weeks or months to ensure treatment success. Recalcitrant cases of anterior uveitis that are unresponsive to conventional therapy may necessitate the use of injectable periocular or intraocular depot steroids, oral corticosteroids (e.g., prednisone 60mg to 80mg daily in divided doses), oral nonsteroidal anti-inflammatory preparations or systemic immunosuppressants such as cyclophosphamide, Trexall (methotrexate, Rheumatrex), azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, interferon or Remicade (infliximab, Janssen).29-34 As a cautionary note, oral corticosteroids and systemic immunomodulatory agents have significant potential for adverse and unforeseen effects. These agents should only be prescribed when the etiology is recognized by clinicians who are well-trained in their use and able to manage their complications. Otherwise, comanagement with a rheumatologist or internist is recommended.

Medical testing is indicated in cases of simultaneous bilateral uveitis (unrelated to trauma), granulomatous uveitis or recurrent unilateral or bilateral uveitis—defined as two or more unexplained incidents.5 A medical workup is particularly relevant when the history or associated symptoms are suggestive of a particular etiology.35 Laboratory testing is not always productive, though the results may be helpful as part of the complete clinical picture. Some of the more common and important tests to consider include: complete blood count with differential and platelets; erythrocyte sedimentation rate; antinuclear antibody; human leukocyte antigen typing; rheumatoid factor; angiotensin-converting enzyme; purified protein derivative with anergy panel; fluorescent treponemal antibody absorption and rapid plasma reagin; and lyme immunoassay.36 Imaging is also part of the medical workup, particularly when the clinical picture is suggestive of ankylosing spondylitis, tuberculosis or sarcoidosis. X-rays of the sacroiliac joint are useful in the diagnosis of ankylosing spondylitis, while a chest radiograph helps to identify tuberculosis or sarcoidosis infiltration into the pulmonary system.36

Clinical Pearls

Cases of acute anterior uveitis as a result of blunt ocular trauma generally resolve without incident and do not recur when properly managed.

A comprehensive, dilated fundus evaluation is mandatory in all cases of uveitis. This is particularly important when visual acuity is significantly diminished. However, this may not be possible on the initial presentation as uveitic eyes are often slow to dilate. A detailed fundus evaluation may have to wait until the first follow-up when the eye is fully cyclopleged.

Many cases of suspected anterior uveitis actually constitute collateral damage from intermediate or posterior uveitis. Such is the case with toxoplas-mosis, for example, where the cells observed in the anterior chamber actually represent “spillover” from posterior segment inflammation.

When in doubt regarding the potency or frequency of topical corticosteroid therapy, it is usually better to overtreat than to undertreat. The potential negative effects associated with corticosteroids (e.g., IOP elevation, cataract formation) often take weeks or months to become apparent, but sight-threatening sequelae of unchecked intraocular inflammation can escalate within hours or days.

Patients with endogenous uveitis (i.e., those cases secondary to infectious or autoimmune disease) often require months of therapy, and some individuals may need to use topical corticosteroids indefinitely to control the inflammation. Physicians who are uncomfortable with such long-term management are advised to refer patients to a specialist with experience in treating uveitis.

While most eye care practitioners are capable of ordering laboratory tests for uveitis directly, it is often more productive to communicate with the patient’s primary care physician before proceeding, so all aspects of the systemic history can be taken into account. Should the patient be diagnosed with a contributory systemic disease, comanagement with the primary care physician, internist or rheumatologist becomes paramount.

Take care to rule out masquerading syndromes such as neoplastic disease in patients presumed to have chronic idiopathic uveitis, especially if recalcitrant.

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